Cellular Adaptation, Hyperplasia

• Cells react to adverse influences through cellular adaptation, reversible injury, and irreversible injury/dying

Cellular Adaptation

• Cells adapt to survive in altered environments
• It is a state between a normal cell and an injured, overstressed cell
• Cells can adapt through hyperplasia, hypertrophy, atrophy, metaplasia, and dysplasia
• Adaptations are reversible changes in number, size, phenotype, metabolic activity, or function in response to environmental changes
• Physiologic adaptations are responses to normal stimulation by hormones or endogenous chemicals (e.g., hormone-induced breast and uterus enlargement during pregnancy)
• Pathologic adaptations allow cells to modulate structure/function and escape injury in response to stress

Hyperplasia

• It is increasing the number of cells in an organ or tissue, potentially increasing volume
• Only cells capable of division can undergo hyperplasia
• Myocytes in the heart and neurons in the brain cannot undergo hyperplasia

Types of Hyperplasia

• Physiological hyperplasia occurs due to hormonal stimulation of female breast epithelium at puberty, or during pregnancy
• Also occurs in the pregnant uterus and normal endometrium after a menstrual cycle
• Compensatory hyperplasia follows removal of part of an organ or a contralateral organ in a paired organ; regeneration of the liver after hepatectomy
• Epidermis regenerates after skin abrasion
• Following nephrectomy on one side, there is hyperplasia of nephrons of the other kidney
• Pathological hyperplasia occurs from excessive hormonal/growth factor stimulation
• Leads to conditions like endometrial hyperplasia, wound healing with granulation tissue, skin warts from human papillomavirus, and prostatic hyperplasia in old age

Hypertrophy

• Increase in cell size leads to an increase in the size of the organ
• Physiologic hypertrophy occurs during pregnancy growth of the uterus, involving both hypertrophy and hyperplasia
• Pathologic hypertrophy is most common stimulus is chronic hemodynamic overload to the heart

Hypertrophy and Hyperplasia

• Hypertrophy and hyperplasia are distinct processes
• They frequently occur together and triggered by the same mechanisms

Atrophy

• Atrophy is acquired loss of size due to a reduction in cell size or number of parenchymal cells in an organ

Types of Atrophy

• Physiologic atrophy includes normal aging tissue processes and loss of endocrine stimulation (arteriosclerosis)
• Atrophy also occurs in lymphoid tissue, lymph nodes, appendix, thymus, gonads after menopause, and the brain with aging
• Pathological atrophy includes starvation, ischemic, neuropathic, endocrine, pressure, and idiopathic atrophy

Metaplasia

• Metaplasia is the reversible change in which one adult cell type is replaced by another adult cell type
• Causes are changes in environment, irritation, inflammation, or nutritional deficiencies

Types of Metaplasia

• The two types of metaplasia are epithelial and mesenchymal
• Squamous metaplasia can occur in the bronchus, uterine endocervix, gallbladder, prostate, renal pelvis, and urinary bladder
• Vitamin A deficiency causes squamous metaplasia in the nose, bronchi, urinary tract, lacrimal, and salivary glands
• Columnar Metaplasia describes instances of intestinal metaplasia in healed chronic gastric ulcers and Barrett's esophagus
• Mesenchymal metaplasia connects tissue, examples are Osseous and cartilaginous metaplasia

Dysplasia

• Dysplasia is disordered cellular development, occurring mainly in the epithelia
• It's non-neoplastic, also referred to as atypical hyperplasia
• It's called carcinoma in situ, if dysplastic changes involve the entire thickness of the epithelium
• Characterized by cellular proliferation and cytological changes
• Results from an increased number of epithelial cell layers, cellular and nuclear pleomorphism
• Increased nucleo-cytoplasmic ratio, nuclear hyperchromatism, or increased mitotic activity
• Examples of dysplastic changes occur include the uterine cervix and respiratory tract

Reversible Injury

• Intracellular edema
• Fatty change
• Hyaline change
• Amyloidosis
• Mucoid degeneration
• Pathologic pigments

Intracellular Edema

• Also called cloudy swelling (hydropic degeneration)
• Accumulation of watery fluid in cells
• It's the most common and earliest form of cell injury
• Caused by bacterial toxins, chemicals, poisons, burns, high fever
• Intravenous administration of hypertonic glucose or saline can also cause intracellular edema
• Impaired regulation of sodium and potassium at the level of cell membrane
• Morphologic change exhibits gross features with cloudy swelling and swollen parenchymal cells

Fatty Change (Steatosis)

• Accumulation of fat in non-fatty cells
• Organ enlarges and becomes yellow, soft, and greasy
• Fatty change appears as clear vacuoles within parenchymal cells
• Liver plays a central role in fat metabolism
• Accumulation of fat in toxic conditions can be very dangerous
• Fatty change can range from mild/reversible to severe/irreversible, leading to injury and cell death

Etiology of Liver Fatty Change

• Conditions that result in excess fat include obesity, diabetes mellitus, or congenital hyperlipidemia
• Liver cell damage can also be caused alcohol, or chronic illnesses such as tuberculosis
• Or acute fatty liver in late pregnancy, hypoxia, hepatotoxins such as carbon tetrachloride,
• Drug-induced liver cell injury such as methotrexate, steroids, halothane anesthetic, or tetracycline
• Leads to enlarged liver with tense, pale-yellow to yellow, greasy to touch characteristics
• Microscopically shows lipid vacuoles in hepatocyte cytoplasm

Fatty Change Heart

• Occurs in two patterns
• Prolonged moderate hypoxia causes intracellular deposits of fat
• Profound hypoxia in diphtheritic myocarditis is a toxin-mediated complication of respiratory illness

Renal Fatty Change

• It's confined to the epithelium of the convoluted tubules
• Affects all structures, including the glomerule in severe poisoning
• Causes include poisons, carbon tetrachloride, phosphorus, chronic alcoholism, infections
• Congestive cardiac failure, severe anemia, ischaemia, diabetes mellitus, or malnutrition and wasting disease can also cause it

Hyaline Change

• Characterized by homogenous, glass-like appearance in H&E-stained sections
• May be intracellular or extracellular
• Hyalinization is the deposition process of hyaline-like homogeneous material that stains intensely with hematoxylin & eosin stain

Intracellular Hyaline

• It is mainly seen in epithelial cells.
• Hyaline degeneration of rectus abdominalis muscle, called Zenker's degeneration, occurring in typhoid fever
• Mallory's hyaline in hepatocytes in alcoholic liver cell injury
• Nuclear/cytoplasmic hyaline inclusions seen in some viral infections
• Russell's bodies represent excessive immunoglobulins

Extracellular Hyaline

• It seen in connective tissues
• Hyaline degeneration in leiomyomas (benign tumor) of the uterus
• Hyalinized old scar of fibro-collagenous tissues
• Hyaline arteriolosclerosis in renal vessels in hypertension and diabetes mellitus
• Hyalinized glomeruli in chronic glomerulonephritis

Mucoid Degeneration

• Mucus containing mucin (glycoprotein), it's secreted by mucous glands
• Cellular injury is characterized by mucin accumulation in intracellular/extracellular loci
• Functional excess of epithelial mucin occurs in catarrhal inflammation of mucous membrane
• Also occurs in obstruction of duct leading to mucocele, cystic fibrosis of the pancreas
• Mucoin secreting tumors lead to mucoid degeneration

Functional Excess of Epithelial Mucin

• Catarrhal inflammation of mucous membranes leads to excess production
• Obstruction duct leads to mucocele
• Cystic fibrosis of the pancreas
• Mucus-secreting tumors

Disturbances of Connective Tissue Mucin

• Mucoid or myxoid degeneration in some tumors
• Tumors include myxomas of the heart, neurofibromas, fibro adenoma of the gland
• Dissecting aneurysm of the aorta occurs in Marfan's syndrome(multi.systemic genetic disorder)
• Myxomatous change in the dermis in myxoedema(sever hypothyroidism)

Pigments

• Pigments are colored substances in living beings
• Classified into endogenous and exogenous categories

Endogenous Pigments

• Melanin
• Haemoprotein derived pigments

Melanin

• Generalised hyperpigmentation is a characteristic
• Addison's disease leads a decrease production of Cortisol and aldesterone from adrenal gland
• Chloasma is a temporary condition typically caused by hormonal change occur in pregnant

Melanin Hyperpigmentation

• Focal hyperpigmentation can lead to Cäfe-au-lait spots, Peutz, or Jeghers syndrome, or Melanosis coli
• Generalised hypopigmentation can lead to Albinism
• Localized hypo pigmentation can lead to Leucoderma, الجذام leprosy, or Vitiligo

Haemoprotein-Derived Pigments

• Haemosiderin (yelloish-brown iron granular pigment that found within cells such as macrophages), is associated with bleeding/breakdown of RBC
• Bilirubin (yellowish pigment) that is made during normal breakdown of the RBC
• Porphyrins
• Lipofuscin (Wear and tear pigment) occurs in Brown atrophy of the heart
• The lipofuscin pigment granules are seen in the cytoplasm of the myocardial fibres, especially around the nuclei

Exogenous Pigments

• Inhaled pigments
• Ingested pigments
• Injested pigments

Inhaled Pigments

• Atmospheric pollutants found in smokers
• Pneumoconiosis: occupational lung diseases
• Anthracosis: deposition of coal

Ingested Pigments

• Argyria: caused by silver compounds which cause brownish pigmentation in the skin, bowel, and kidney
• Burtonian Lines: caused by chronic lead poisoning are blue lines on the teeth at the gumline
• Melanosis coli: caused by chronic laxative stimulate evacuation of the bowels
• Carotenaemia: caused by yellowish-red colouration of the skin resulting from ingestion of carrots contains carotene
• (Tattooing): India ink, cinnabar and carbon deposited in dermis

Amyloid Degeneration

• Extracellular deposition of fibrillar proteinaceous substance called amyloid
• Amyloid is a waxy substance' composed of an abnormal protein
• Occurs around the supporting fibres of blood vessels and basement membranes
• Associated with a number of inherited and inflammatory disorders

Fibril Proteins

Non-Fibrillar Components

• Amyloid P (AP)-component
• Apolipoprotein-E (apoE)
• .a-1 anti-chymotrypsin
• .Protein X

Pathogenesis of Amyloidosis

• Result of immunologic mechanisms
• Caused by an abnormality in plasma cell found in the bone marrow
• The source marrow has a dysfunction to produce abnormal forms of light chain protein
• The abnormal cells enter bloodstream and can form amyloid deposites
• More than 20 (at last count, 23) different proteins can aggregate and form fibrils with the appearance of amyloid
• The dye Congo red Stain is commonly used to identify amyloid desposits in tissues

Classification of Amyloidosis

• Based on cause: primary and secondary
• Primary: with unknown cause and the deposition is in the disease, itself
• Secondary: complication of some underlying known disease
• Based on extent of amyloid deposition it can be systemic or localized
• Systemic (generalised): affecting multiple organs
• Localized: 1 or 2 organs or sites
• Based on histological distribution

Pathological Effect of Amyloid

• Pressure on adjacent cells, atrophy, blood vessels that affect narrowing increased permeability
• Transudation of protein out of vessels

Morphologic Features of Amyloidosis of Organs

• Amyloid deposits appear at the contacts between the vascular spaces and parenchymal cells
• Morphology manifests an in enlarged affected organ that is pale and rubbery
• Cut surface shows firm, waxy and translucent parenchyma
• Microscopically is deposited amyloid are in the extracellular of area like walls of blood vessel